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Two DNA binding domains of MGA act in combination to suppress ectopic activation of meiosis-related genes in mouse embryonic stem cells
STEM CELLS ( IF 5.2 ) Pub Date : 2021-07-05 , DOI: 10.1002/stem.3433
Kousuke Uranishi 1 , Masataka Hirasaki 2 , Yuka Kitamura 1 , Yosuke Mizuno 3 , Masazumi Nishimoto 1, 3 , Ayumu Suzuki 1 , Akihiko Okuda 1
Affiliation  

Although the physiological meaning of the high potential of mouse embryonic stem cells (ESCs) for meiotic entry is not understood, a rigid safeguarding system is required to prevent ectopic onset of meiosis. PRC1.6, a non-canonical PRC1, is known for its suppression of precocious and ectopic meiotic onset in germ cells and ESCs, respectively. MGA, a scaffolding component of PRC1.6, bears two distinct DNA-binding domains termed bHLHZ and T-box. However, it is unclear how this feature contributes to the functions of PRC1.6. Here, we demonstrated that both domains repress distinct sets of genes in murine ESCs, but substantial numbers of meiosis-related genes are included in both gene sets. In addition, our data demonstrated that bHLHZ is crucially involved in repressing the expression of Meiosin, which plays essential roles in meiotic entry with Stra8, revealing at least part of the molecular mechanisms that link negative and positive regulation of meiotic onset.

中文翻译:

MGA的两个DNA结合域共同作用抑制小鼠胚胎干细胞减数分裂相关基因的异位激活

尽管尚不清楚小鼠胚胎干细胞 (ESC) 对减数分裂进入的高潜力的生理意义,但需要一个严格的保护系统来防止异位发生减数分裂。PRC1.6 是一种非经典的 PRC1,以其分别抑制生殖细胞和 ESC 中的早熟和异位减数分裂发作而闻名。MGA 是 PRC1.6 的一个支架组件,具有两个不同的 DNA 结合结构域,称为 bHLHZ 和 T-box。然而,目前尚不清楚此功能如何影响 PRC1.6 的功能。在这里,我们证明了这两个域都抑制小鼠 ESC 中不同的基因组,但大量减数分裂相关基因包含在两个基因组中。此外,我们的数据表明,bHLHZ 在抑制Meiosin的表达中起着至关重要的作用。,它在与Stra8的减数分裂进入中起重要作用,揭示了将减数分裂开始的负调控和正调控联系起来的至少部分分子机制。
更新日期:2021-07-05
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